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BACKGROUND The unit equivalence between the two main Botulinum neurotoxin A (BoNTA) preparations, Dysport (Ipsen Ltd., Slough, Berkshire, UK) and BOTOX (Allergan Inc., Irvine, CA), is a matter of
discussion. The UK assay used to test Dysport is more sensitive than the U.S. assay used for BOTOX,
resulting in a different efficacy per unit in both formulations. Ratios ranging from 6:1 to 1:1 can be found
in the literature, but the more recently published literature suggests that 1 unit of BOTOX is equivalent to
approximately 2 to 4 units of Dysport (ratio 2:14:1).
OBJECTIVE Because the number of BoNTA treatments is constantly increasing, these differences warrant a systematic review of published evidence about the unit equivalence of UK and U.S. formulations.
METHODS The review is based on a detailed literature research in all relevant databases (MEDLINE,
PubMed, Cochrane Library, specialist textbooks).
RESULTS The present review supports the recent assumption that dose ratios of less than 3:1
(e.g., 2.5:1 or even 2:1) between Dysport and BOTOX are probably more suitable.
CONCLUSIONS The current evidence is still insufficient, and further investigation of lower dose ratios is
recommended.
The authors have indicated no significant interest with commercial supporters.
Heidelberg, Germany
& 2008 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.
ISSN: 1076-0512 Dermatol Surg 2009;35:18 DOI: 10.1111/j.1524-4725.2008.34375.x
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U N I T E Q U I VA L E N C E O F B o N TA F O R M U L AT I O N S
D E R M AT O L O G I C S U R G E RY
Methods
This review is based on a detailed literature research
in all relevant databases: MEDLINE (National
Library of Medicine), PubMed (National Library
of Medicine), the Cochrane Library, and specialist
textbooks. Selected key words were: BONTA or
BOTULINUM TOXIN TYPE A and POTENCY
(11 hits), BONTA or BOTULINUM TOXIN
TYPE A and DYSPORT and BOTOX (13 hits),
BONTA or BOTULINUM TOXIN TYPE A and
DOSE-RESPONSE RELATIONSHIP and COM-
TABLE 1. Level of Evidence (According to Sackett et al.18) of the Studies Quoted in Results
Evidence
level
Ia
Ib
IIa
Explanation
Studies
IIb
IIc
Outcomes research
Expert opinion
SR, systematic review; RCT, randomized controlled trial; CI, confidence interval; CS, cohort study.
Results
Cosmetic Applications (Hyperfunctional Lines)
The majority of clinical trials recommend a unit
equivalence of 3:1 based on the aforementioned
Cochrane review.15 This ratio consistently yields
favorable results with low toxicity in the treatment
of forehead wrinkles.19,20
In a randomized controlled double-blind split-face
trial,21 a dosage scheme of 3:1 yielded more
pronounced effects of Dysport than of BOTOX in
3 5 : 1 : J A N U A RY 2 0 0 9
U N I T E Q U I VA L E N C E O F B o N TA F O R M U L AT I O N S
These four studies are the only ones that fulfilled the
Cochrane criteria for evidence-based medicine.
Although the authors of these studies all concluded
that the effects of the two products were equivalent,
the effects and side effects of Dysport were consistently higher in all four studies and at both dose
ratios. These differences were not statistically
significant but strongly suggest that even 3:1 is
still too high a conversion ratio. Sampaio and
colleagues themselves concluded that 3:1 was more
appropriate than 4:1 but that the products were not
equivalent at this ratio.
D E R M AT O L O G I C S U R G E RY
In treatment of anal fissures, Brisinda and colleagues35 found no difference in efficacy and toxicity
of Dysport and BOTOX in 100 patients employing
a 3:1 unit equivalence. By contrast, Bihari16 found
a higher efficacy of BOTOX after a switch from
Dysport at a 4:1 or even 5:1 dosage ratio in a cohort
of 48 patients with blepharospasm, cervical dystonia,
or hemifacial spasm. Quite astoundingly, the rate of
side effects was higher with Dysport. A few methodological questions have to be mentioned in a critical
light: First, the patients were a sample from a population of undefined size. The background of the
study was the temporary nonavailability of Dysport
in Hungary, and patients were offered the choice of
switching to BOTOX or waiting until Dysport
became available again. The number of patients who
opted for the latter is undisclosed, as is the number of
patients who opted for BOTOX but refused to participate in the study. Moreover, the absolute point
differences in TWSTRS pain score are analyzed
without information about the baseline values,
making it hard to judge the extent of improvement
objectively. Clinical improvement was exclusively
Hyperhidrosis
Based on a 4:1 conversion factor, Simonetta-Moreau
and colleagues38 found a higher efficacy of Dysport
in palmar hyperhidrosis. This was paired with a
somewhat higher toxicity (weakness of thumb-index
pinch), indicating that a lower ratio would be
preferable.
A recent study analyzing the anhidrotic area in 20
patients with forehead hyperhidrosis39 suggested a
greater diffusion area of Dysport, possibly hindering
the exact localization of the desired effect. As an
accompanying result, the study failed to demonstrate differences in efficacy between both formulations at ratios of 2.5:1, 3:1, and 4:1, suggesting that
a ratio of 2.5:1 is at least equipotent.
Finally, Talarico-Filho and colleagues40 found no
difference in efficacy at a 3:1 ratio in the treatment
of axillary hyperhidrosis in 10 patients.
Experimental Evidence
Preliminary data on action halos41,42 (i.e.,
anhidrotic circles around the site of injection) seen in
the forehead of human subjects support a ratio of less
than 3:1. This is also the case in another human
model, the Extensor Digitorum Brevis compound
action potential, on which an extensive series of
comparative measurements was recently performed.43
Discussion
The effect of BoNTA as a muscle-relaxing agent is
undisputed in cosmetic and medical settings. As
outlined in the introduction, once physicians realized
that there was a difference in unit potency between
the two BoNTA assays, a conversion factor of 4 to
5:1 was assumed. This thought has proved surprisingly persistent, despite the fact that extensive comparison of the assays in different laboratories and
comparative clinical trials conducted in accordance
with Cochrane standards of evidence-based medicine
suggest that 3:1 is a more appropriate conversion
ratio. However, lower ratios have not yet been tested
in such head-to-head trials, and the data from these
studies indicate that 3:1 is still too high. The overwhelming majority of published studies support this
ratio as a ceiling, and it should not be exceeded.
Instead, a lower ratio of 2.5:1 or even 2:1 deserves
further research, because present evidence suggests
that this is probably sufficient in terms of efficacy
and should therefore be preferred because of
lower treatment cost and a broader safety margin.
Also, a meta-analysis15 has shown that the two
formulations are not bioequivalent regardless of
the dose relationship and that Dysport and BOTOX
3 5 : 1 : J A N U A RY 2 0 0 9
U N I T E Q U I VA L E N C E O F B o N TA F O R M U L AT I O N S
D E R M AT O L O G I C S U R G E RY
References
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3 5 : 1 : J A N U A RY 2 0 0 9
U N I T E Q U I VA L E N C E O F B o N TA F O R M U L AT I O N S
40. Talarico-Filho S, Mendonca DO, Nascimento M, et al. A doubleblind, randomized, comparative study of two type A botulinum
toxins in the treatment of primary axillary hyperhidrosis.
Dermatol Surg 2007;33(1 Spec No.):4450.
D E R M AT O L O G I C S U R G E RY
42. de Almeida A, Marques J, de Almeida J, et al. Pilot study comparing the diffusion characteristics of two formulations of
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American Academy of Dermatology: 64th Annual Meeting;
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